McGovern Naomi, Schlitzer Andreas, Gunawan Merry, Jardine Laura, Shin Amanda, Poyner Elizabeth, Green Kile, Dickinson Rachel, Wang Xiao-Nong, Low Donovan, Best Katie, Covins Samuel, Milne Paul, Pagan Sarah, Aljefri Khadija, Windebank Martin, Miranda-Saavedra Diego, Larbi Anis, Wasan Pavandip Singh, Duan Kaibo, Poidinger Michael, Bigley Venetia, Ginhoux Florent, Collin Matthew, Haniffa Muzlifah
Institute of Cellular Medicine, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; Singapore Immunology Network, Agency for Science Technology and Research (A-Star), 8A Biomedical Grove, Immunos, Singapore 138648.
Singapore Immunology Network, Agency for Science Technology and Research (A-Star), 8A Biomedical Grove, Immunos, Singapore 138648.
Immunity. 2014 Sep 18;41(3):465-477. doi: 10.1016/j.immuni.2014.08.006. Epub 2014 Sep 4.
Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141(hi)XCR1⁺ CLEC9A⁺ DCs and CD1c⁺ DCs are murine CD103⁺ DCs and CD64⁻ CD11b⁺ DCs. In addition, human tissues also contain CD14⁺ cells, currently designated as DCs, with an as-yet unknown murine counterpart. Here we have demonstrated that human dermal CD14⁺ cells are a tissue-resident population of monocyte-derived macrophages with a short half-life of <6 days. The decline and reconstitution kinetics of human blood CD14⁺ monocytes and dermal CD14⁺ cells in vivo supported their precursor-progeny relationship. The murine homologs of human dermal CD14⁺ cells are CD11b⁺ CD64⁺ monocyte-derived macrophages. Human and mouse monocytes and macrophages were defined by highly conserved gene transcripts, which were distinct from DCs. The demonstration of monocyte-derived macrophages in the steady state in human tissue supports a conserved organization of human and mouse mononuclear phagocyte system.
树突状细胞(DCs)、单核细胞和巨噬细胞是在免疫和耐受中起关键作用的白细胞。DC网络在进化上是保守的;人类组织中CD141(hi)XCR1⁺ CLEC9A⁺ DCs和CD1c⁺ DCs的同源物是小鼠CD103⁺ DCs和CD64⁻ CD11b⁺ DCs。此外,人类组织中还含有CD14⁺细胞,目前被指定为DCs,其小鼠对应物尚不清楚。在这里,我们证明了人类真皮CD14⁺细胞是单核细胞来源的巨噬细胞的组织驻留群体,半衰期短于6天。人类血液CD14⁺单核细胞和真皮CD14⁺细胞在体内的下降和重建动力学支持了它们的前体-子代关系。人类真皮CD14⁺细胞的小鼠同源物是CD11b⁺ CD64⁺单核细胞来源的巨噬细胞。人类和小鼠的单核细胞和巨噬细胞由高度保守的基因转录本定义,这些转录本与DCs不同。在人类组织稳态中单核细胞来源巨噬细胞的证明支持了人类和小鼠单核吞噬细胞系统的保守组织。